The role of histamine in anaphylactic reaction is well established. Information concerning the role of histamine in modulating neuronal and cellular functions through specific H1 and H2 histamine receptors are now accumulating. The study of the mechanism of histamine release from rat peritoneal mast cells will enable us to understand the mechanism of neuropeptide secretion and the mechanism by which eurkaryotic membrane assembly can occur. The generation of de novo membrane has been shown to occur following granule activation in rat peritoneal mast cells. The rapid assembly of this new membrane may provide a model for studying membrane formation in eukaryotic cells. We have localized a high level of calcium and a calmodulin-like activity in the granule matrix. The role of calcium and calcium-binding protein in promoting membrane fusion has been suggested before. Their presence here might be to enhance the fusion of the newly assembled membrane with the plasma membrane and thus facilitate exocytosis. In order to firmly establish our hypothesis that de novo membrane generation occurs during granule activation, we will attempt to demonstrate that the swelling of the granule matrix and the expansion of the perigranular membrane occurs prior to the fusion of the perigranular membrane with the plasma membrane. It is also important to be able to isolate unactivated quiescent granules for phospholipid determination such that the source of the new membrane can be verified.